NON-ACIDIC CYCLOPENTANE HEPTANOIC ACID, 2-CYCLOALKYL OR ARYLALKYL DERIVATIVES AS THERAPEUTIC AGENTS

• US 20090227672A1
• Filed: 12/19/2008
• Published: 09/10/2009
• Est. Priority Date: 09/21/1992
• Status: Active Grant

• Current Assignee: David F. Woodward, Michael E. Garst, Robert M. Burk, Steven W. Andrews
• Original Assignee: David F. Woodward, Michael E. Garst, Robert M. Burk, Steven W. Andrews
• Inventors: Garst, Michael E., Woodward, David F., Burk, Robert M., Andrews, Steven W.
• Granted Patent: US 8,017,655 B2
• Time in Patent Office: Days
• US Class Current: 514/530
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/5585 having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
• CPC Class Codes: A61K 31/559 having heterocyclic rings containing hetero atoms other than oxygen
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: C07C 215/42 having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
• CPC Class Codes: C07C 235/34 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 247/10 and containing rings
• CPC Class Codes: C07C 255/36 the carbon skeleton being further substituted by hydroxy groups
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 35/21 polycyclic, at least one hydroxy group bound to a non-condensed ring
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof

Abstract

The present invention provides cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compounds, which may be substituted in the 1-position with amino, amido, ether or ester groups, e.g., a 1-OH cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compound. The cyclopentane heptanoic acid, 2-(cycloalkyl or arylalkyl) compounds of the present invention are potent ocular hypotensives, and are particularly suitable for the management of glaucoma. Moreover, the cyclopentane heptanoic, 2-(cycloalkyl or arylalkyl) compounds of this invention are smooth muscle relaxants with broad application in systemic hypertensive and pulmonary diseases; smooth muscle relaxants with application in gastrointestinal disease, reproduction, fertility, incontinence, shock, etc.

Claims

1. A method of treating glaucoma and ocular hypertension which comprises topically administering to the affected eye a therapeutic effective amount of a compound of formula:

2. The method of claim 1, wherein R¹ is selected from the group consisting of H, CH₃, CH(CH₃)₂ and C(CH₃)₃.

3. The method of claim 1, wherein R¹ is selected from the group consisting of Na⁺ and CH₃ N⁺(CH₂OH)₃.

4. The method of claim 1, wherein R² is Cl.

5. The method of claim 2, wherein R² is CF₃.

6. The method of claim 1, wherein between about 0.001 and about 1000 μ

g/eye of a compound of formula (I) is administered.

7. The method of claim 6, wherein between about 0.01 and about 100 μ

g/eye of a compound of formula (I) is administered.

8. The method of claim 6, wherein between about 0.05 and about 10 μ

g/eye of a compound of formula (I) is administered.

9. A topical ophthalmic composition for treatment of glaucoma and ocular hypertension in primates, comprising topically a therapeutically effective amount of a compound of formula:

10. The composition of claim 9, wherein R¹ is selected from the group consisting of H, CH₃, CH(CH₃)₂ and C(CH₃)₃.

11. The composition of claim 9, wherein R¹ is selected from the group consisting of Na⁺ and

CH₃N⁺(CH₂OH)₃.

12. The composition of claim 9, wherein R² is Cl.

13. The composition of claim 9, wherein R² is CF₃.

16. The composition of claim 9, wherein between about 0.05 and about μ

g/eye of a compound of formula (I) is administered.

14. (canceled)

15. (canceled)

17. A method of treating glaucoma and ocular hypertension, which comprises topically administering to the affected eye a therapeutically effective amount of a compound of formula:

18. The method of claim 17, wherein R² is Cl.

19. The method of claim 17, wherein R² is CF₃.

20. The method of claim 17, wherein between 0.001 and about 1000 μ

g/eye of a compound of formula (I) is administered.

21. A method of treating glaucoma and ocular hypertension which comprises topically administering to the affected eye a therapeutically effective amount of cyclopentane heptenoic acid, 5-cis-2-(3-α

-hydroxy-4-m-chlorophenoxy-1-trans-butenyl)-3,5-dihydroxy 1_a, 2_α

, 3_a, 5_a].

22. A method of treating glaucoma and ocular hypertension which comprises topically administering to the affected eye a therapeutically effective amount of fluprostenol.

23. (canceled)